Hypoxia results from long-term anti-angiogenic therapy and can stimulate hypoxia-inducible factors (HIFs). HIF-induced hy-poxia signaling is involved in various steps in tumor invasive-metastatic cascade. On the one hand, HIFs regulate epithelial-mesenchy-mal transition. On the other hand, the characteristics of pericytes around vessels and the links among endothelial cells can change;thus, tumor cells can more easily intravasate into blood vessels, survive in peripheral blood, and then reach specific organs, ultimately resulting in metastasis. This review discusses the emerging mechanisms of long-term anti-angiogenic therapy and the occurrence of metastasis.

Dedifferentiated chondrosarcoma(DDCS)comprises approximately 10%of all chondrosarcomas and has the worst outcome with a 5-year survival of 10%.The preferred localizations are the femur,humerus and pelvis.DDCS represents a special form of chondrosarcoma characterized by the presence of well-differentiated cartilaginous component in juxtaposition with malignant mesenchymal tumor of high-malignancy grade.The diagnosis of DDCS is highly complicated,requiring detailed radiological and histopathological evaluation as well as precise bioptic technique.The dedifferentiated component is typically a high-grade sarcoma(usually grade 3 or 4),which can be either an osteosarcoma,a malignant fibrous histiocytoma or an anaplastic spindle cell sarcoma.In approximately one-third of the radiographs,one-third of the MR images,and one-half of the CT scans, the tumors demonskates bimorphic features.Recently,array-based comparative genomic hybridization(array-CGH)studies have been performed on frozen chondrosarcoma(including DDCS)specimens.There is a statistically significant association between high-grade tumor(grade Ⅲ and dedifferent ated)and the recurrent genetic deletions at 5q14.2～q21.3,6q16～q25.3,9p24.2～q12,and 9p21.3.One of the most commonly deleted regions of DDCS involved chromosome 9.Earlier investigations of DDCS showed p53 mutation and p53-LOH in the anaplastic component.It is also accompanied by Rt-LOH.P161NK4 and E-cadherin promotor methylation were observed in the low grade chondroid compartment of DDCS.While p161NK4,FHIT,and E-cadherin were methylated in highly malignant osteosarcomatous compartment of the tumor.Surgical resection of the tumor within wide or radical margins is the most important treatment.The value of neoadjuvant or adjuvant therapy remain uncertain.Several new drug targets have been identified and phase Ⅱ studies are currently ongoing.Current phase Ⅱ trials open for DDCS patients used the following medicine:apomab(proapoptotic selective agonist of Ap02L/TRAIL death receptor),perifosine(serine/threonine kinase Akt inhibitor),dasatinib(multitargeted small-molecule tyrosine kinase inhibitor),and the combination of gemcitabine and docetaxel.More recently,several phase Ⅰ studies have reported incidental responses of DDCS to newer targeted agents,such as histone deacetylase and vascular endothelial growth factor antisense oligodeoxynucleotide.The prognosis for patients with DDCS remains poor. The poor prognosis of the DDCS is determined by nonchondroid high grade component caused by invasive growth and formation of metastases.Therefore,early diagnosis and prompt surgical treatment may improve the outcome.

AIM: To study the pharmacological effect of Weichangshu (WCS) (Rhizoma coptidis, Fructus Evodiae., etc.) on rodent gastrointestinal function and gastric mucosa, and to analyze its analgesic and antidiarrheal mechanism. METHOD: Mouse's hypermobility induced by neostigmine and its gastric emptying were treated by WCS in comparison with normal subjects, rat's gastric ulcer induced by absolute ethanol, diarrhea induced by castor oil, pain induced by acetic acid and rat's gastric secretion and absorption were observed. RESULTS: The experimental results showed that WCS did not affect normal mouse's intestinal propulsion but significantly antagonized neostigmine induced intestinal propulsion and inhibited the gastric mucosa injure and decreased the frequency of the writhe and limited diarrhea. CONCLUSION: WCS has power to recover gastrointestinal function and lessen gastric mucosa injury and has analgesic and antidiarrheal effect.

[Objective]To evaluate the outcome on patients with primary infection of intervertebral space of the thoracolumbar spine following combined one-stage debridement,strut grafting and internal fixation.[Method] From May 1999 to February 2006,18 patients with spontaneous infection of intervertebral space were analyzed retrospectively.These infections occurred at thoracic spine in 3 cases(16.7%),thoracolumbar junction in 2 cases(11.1%),lumbar spine in 10 cases(55.5%),and lumbosacral junction in 3 cases (16.7%).Their clinical data and outcome were studied.None of all had previous spinal surgery or spinal injection,and their diagnosis were confirmed by histopathology after surgery.All patients were treated by one-stage debridement,strut grafting and internal fixation after failure of nonsurgical treatment.Antibiotics was used following debridement in the infection sites,and was continued to be administered after surgery.Patients were evaluated before and after surgery in terms of pain,neurologic level,sagittal spinal balance,and radiologic fusion.[Result]Postoperatively,all patients experienced significant relief of symptoms,and no fever.Six patients showed improved neurological status(at least one grade improvement on Frankel's functional classification).Only 3 of 18 cases had a positive culture result that pathogen identified Staphylococcus aureus.Histological examination of the specimen after surgery revealed that inflammation occurred in all patients,but no evidence of tuberculosis.The period of follow-up ranged 13 to 45 months with a mean of 26 months.No evidence of recurrence or residual infection was observed in any patient.Postoperative radiological evaluation revealed that implants were stable,there was no phenomena of prosthesis subsidence,hook dislodgment and failure restoration of spinal segments height.Solid bony fusion was obtained in all patients.Eight patients were misdiagnosed for spinal tuberculosis.[Conclusion] One-stage eradication of the infection,strut grafting and internal fixation are effective treatments for primary infection of intervertebral space.The presence of the instrumentations at the site of infection has no negative influence on the course of infection healing.

[Objective]To evaluate the diagnostic strategy for bone metastasis from unknown primary. [Method]One hundred and twenty five patients with unknown primary bone metastasis were treated from June 2003 and December 2006.The distribution of bone metastasis while initial diagnosis mainly focused on spine,sacrum,pelvis,femur and humerus.The diagnostic strategy contained a series of physical examination,laboratory test,imaging study and pathological examination.[Result]The primary tumor was found in 70.4% cases,while 40% was in the lung,8% in kidney,5.6% in prostate,4.8% in liver,4% in breast,both 2.4% in thyroid and gastric,and 3.2% in other visceras.The physical examination revealed the occult primary site of the malignant tumor in only 9.6% cases.Although,43.2% patients had higher level of tumor antigen,but most of them were non-specific.Sixty percent of primary tumor was found by various imaging studies including plain radiograph,computed tomography and ultrasound.The pathological result after biopsy or operation identified or suggested the primary tumor in 66.4% cases.The one year survival rates after diagnosis were 58.57% and 22.93% in patients of bone metastasis with known and unknown origin,respectively.[Conclusion]The primary tumor can be diagnosed in most bone metastasis patients with no cancer history after careful examination,and patients will get benefit on survival time for targeted treatment.

[Objective] A retrospective study of patients with osteosarcoma in the proximal humerus was carried out to evaluate the effect of limb salvage surgery.[Methods]Thirty-eight patients received neoadjuvant chemotherapy and limb salvage were included in the study.Extraarticular or intraarticular resections of the proximal humerus were performed in 5 patients and 33 patients,respectively.The reconstructions included 31 custom-made prosthetic replacements,4 allograft prosthetic composites,1 bone cement spacer,and 2 autografts.The image files of patients receiving intraarticular resection were studied to identify tumor invasion of glenoid and deltoid muscule.[Results]Local recurrence encountered in 5 patients(13.2%)including 1 with extraarticular resection and 4 with intraarticular resection.In patients with intraarticular resection,image study revealed gleoid and deltoid muscule invasion occurred in 7 patients,of whom only 4 had local recurrence.The overall 5-year survival rate was 56.4%,and the disease-free survival rate was 40.5%.Complication rate of limb salvage surgery was 18.4%,which included two autograft bone fractures,one embolism of upper limb artery combined with radial nerve injury,and 4 shoulder joint instabilities.The functional outcomes of mean MSTS 93 score was 22.7 points(75.6%).The active external extension of shoulder joint was restricted in patients with extraarticular resection of no more than 30 degrees,and in patients with intraarticular resection of mean 45 degrees.[Conclusion]Acceptable oncological result and better function could be obtained after intraarticular resection of osteosarcoma in proximal humerus if glenoid or deltoid muscle invasion was not found on image study.Prosthetic replacement in these patients had lower complication rate,and better upper limb or hand function.

Objective To investigate the feasibility of the gene therapy on angiogenesis after myocardial infarction in rats.Methods Thirty-six male SD rats,after the ligation of left anterior descending coronary artery,were divided into 2 groups as experimental and control one.Expressions of VEGF were measured by RT-PCR and Immunohistochemistry(IHC).Angiogenesis and capillary density were evaluated by HE stain,and qualitative and quantitative analysis were carried out.The adverse effects were tested after injection of pVEGF165-PLGA nanoparticle.Results Compared with control groups,ischemic myocardial cells persistently and stably expressed VEGF in experimental group;Vascular endothelial cells actively proliferated,and the effect of angiogenesis was significant;48 hours later,nanoparticles were observed in myocardial cells.Conclusion Injection of with pVEGF165-PLGA nanoparticle,it can stimulate effective host-derived angiogenesis,which results in the prevention of impaired cardiac muscle after myocardial infarction.It may be an effect way to treat MI.

We reported a case of adult Drosophila melanogaster parasitized in nasal cavity of a 81-year-old woman who was living in Xuancheng City, Anhui Province now. She was admitted for treatment of cerebral infarction and water accumulation in the lungs in 2014 June. The patient was also suffering from secretory otitis media, a history of hypertension and heart stents were placed in 2007. A foreign body was found in the left nasal cavity during the preoperative examination process, and then the part of the inflammatory tissue was removed through the nasal endoscopy, and sent to our department for identification. There are three adults of Drosophila in paraffin-embedded biopsy specimens. The parasites length is approximately 3mm, with huge red compound eyes. The end of the body is tip, with 5 ring lines in back, has no dark spots. The abdomen of the parasites have seven sections. Tarsus of foot I have no sex comb on base, and they are male adult of Drosophila melanogaster after identification. After a thorough reviewing of medical history, we knew the patient began to sneeze violently and frequently six years ago. But there was no clear or purulent nasal discharge flowing, therefore did not attract attention. After removing the parasites the sneezing symptoms were relieved, and had no abnormal symptoms in the follow-up 6 months.
Aged, 80 and over ; Animals ; Drosophila melanogaster ; growth & development ; Endoscopy ; Female ; Foreign Bodies ; diagnosis ; parasitology ; Humans ; Male ; Nasal Cavity ; parasitology

To improve the preparation speed and quality of moxa cone, a mould for preparation of moxa cone was designed and applied in moxibustion. It consists three parts: a foundation (a flat-bottomed circular cylinder hollow in center), a moxa cone forming tube (a hollow column encircled by two semi-cylinders with symmetrical shape and size, and was inserted in the internal cavity of the foundation); and a compression rod (a solid cylinder used for compressing moxa placed in moxa cone forming tube). The mould is practical, simple, and convenient and can effectively speed up the preparation of moxa cone, and it is safe in application. Moreover, the obtained moxa cones are regular in shape, uniform in dosage and size, dense in texture, and convenient to pack, store and carry.

Objective:To clarify the effects of the BMP receptor inhibitor LDN-193189 in the dedifferentiated chondrosarcoma (DDCS) cell line NDCS-1 and to explore the anti-tumor mechanism of LDN-193189 in DDCS. Methods:NDCS-1 was treated with 5 nmol/L of LDN-193189. MTT assay and clone formation experiments were used to verify that LDN-193189 suppressed cel proliferation. Transwel and wound healing tests were performed to demonstrate that LDN-193189 inhibited cell invasion. Western blot detection was used to show that LDN-193189 inhibited the suppression of BMPR2, p-Smad1/5, and RUNX2 protein expression. Results:The BMPR2 signaling pathway was inhibited by LDN-193189;thus, cell viability and invasion were significantly suppressed. Conclusion:LDN-193189 induces the inhibition of progression in vitro via the BMPR2-p-Smad1/5-RUNX2 signaling pathway in the human DDCS cell line NDCS-1.